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Galijatovic, Alema; Otake, Yoko; Walle, U K; Walle, Thomas

doi:10.1023/a:1011019417236

Cited by 101 publications

(21 citation statements)

References 20 publications

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“…The flavone chrysin increased mRNA-levels, protein expression and enzyme activity of the UGT isoform UGT1A1 in intestinal Caco-2 and hepatic Hep G2 cells after an incubation time of several days [213][214][215]. Other flavones like acacetin, apigenin, baicalein, diosmetin and luteolin as well as the flavonols quercetin and kaempferol increased either activity or transcriptional activation of UGT1A1 in Hep G2 cells [199,200].…”

Section: Interaction Of Flavonoids With Phase II Conjugation Enzymesmentioning

confidence: 99%

The Potential of Flavonoids to Influence Drug Metabolism and Pharmacokinetics by Local Gastrointestinal Mechanisms

Cermak¹,

Wolffram²

2006

CDM

111

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In recent years, public and scientific interest in plant flavonoids has tremendously increased due to postulated health benefits. Whereas the amount of flavonoids ingested with the regular diet is rather low, the use of supplements enriched with these polyphenolics is becoming increasingly popular. This raises concerns about possible interactions of flavonoids with therapeutic drugs, because both are xenobiotics and, thus, share at least partially the same metabolic pathways. A number of in vitro studies have shown effects of flavonoids on enzymes involved in xenobiotic metabolism, like cytochrome P450 monooxygenases and phase II conjugation enzymes, or on membrane transporters involved in drug excretion. Several investigations have also reported changes of drug bioavailability by certain flavonoids. This article attempts to present an overview of flavonoid effects on pathways involved in drug metabolism. It focuses on phase I and phase II enzymes as well as on transporters involved in drug metabolism which are expressed in the gastrointestinal tract.

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Section: Interaction Of Flavonoids With Phase II Conjugation Enzymesmentioning

confidence: 99%

The Potential of Flavonoids to Influence Drug Metabolism and Pharmacokinetics by Local Gastrointestinal Mechanisms

Cermak¹,

Wolffram²

2006

CDM

111

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“…Studies have shown that human mammary cells have the capacity to metabolize the parent compound PhIP as well as the hydroxylated intermediates [50][51][52]. PhIP is glucuronidated by UGT1A1 in the human colon carcinoma cell line Caco2 [53] and human prostate cells have also been shown to metabolize PhIP ( [54,55], Kulp, personal observations). The metabolic pathways and the metabolites produced during PhIP bioactivation in these target organs have not been fully determined.…”

Section: Introductionmentioning

confidence: 99%

PhIP metabolites in human urine after consumption of well-cooked chicken

Kulp

Knize

Fowler

et al. 2004

Journal of Chromatography B

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“…Considering that SN50 (a NF-kB translocation inhibitor) could enhance the induction of UGT1A1 by apigenin, it was believed that UGT1A1 induction by apigenin might be associated with NF-kB translocation 85 . In addition to apigenin, quercetin was also shown to markedly increase the glucuronidation activity in Caco-2 cells 80 . The significant increase in glucuronidation activity might result from increasing expression levels of UGT1A6 (at 50 μM of quercetin) and UGT1A1 86,87 .…”

Section: Effects Of Flavonoids On Phase II Enzymesmentioning

confidence: 97%

“…It suggested that flavonoids could play an important role in modulation of sex hormones in humans and provide us with a possible means to prevent and manage prostate cancers. In addition, chrysin was reported to be able to induce UGT1A1 specifically, both in Caco-2 and HepG2 cells 78,79,80 . However, UGT1A6, UGT1A9 and UGT2B7 were not affected by the chrysin treatment 80 .…”

Section: Effects Of Flavonoids On Phase II Enzymesmentioning

confidence: 99%

“…In addition, chrysin was reported to be able to induce UGT1A1 specifically, both in Caco-2 and HepG2 cells 78,79,80 . However, UGT1A6, UGT1A9 and UGT2B7 were not affected by the chrysin treatment 80 . Further study from the same group showed that induction of UGT1A1 by chrysin was not dependent on aryl hydrocarbon receptor (AhR) since galangin and isorhamnetin, both of which are inducers of CYP1A1 via AhR, did not display any induction of UGT1A1 81 .…”

Section: Effects Of Flavonoids On Phase II Enzymesmentioning

confidence: 99%

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Mutual interactions between flavonoids and enzymatic and transporter elements responsible for flavonoid disposition via phase II metabolic pathways

Jiang

2012

RSC Adv.

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Flavonoids, existing mainly as glycosides in nature, have multiple “claimed” beneficial effects in humans. Flavonoids are extensively metabolized in enterocytes and hepatocytes by phase II enzymes such as UGTs and SULTs to form glucuronides and sulfates, respectively. These glucuronides and sulfates are subsequently excreted via ABC transporters (e.g., MRP2 or BCRP). Therefore, it is the interplay between phase II enzymes and efflux transporters that affects the disposition of flavonoids and leads to the low bioavailability of flavonoid aglycones. Flavonoids can also serve as chemical regulators that affect the activity or expression levels of phase II enzymes including UGTs, SULTs and GSTs, and transporters including P-gp, MRP2, BCRP, OATP and OAT. In general, flavonoids may exert the inhibitory or inductive effects on the phase II enzymes and transporters via multiple mechanisms that may involve different nuclear receptors. Since flavonoids may affect the metabolic pathways shared by many important clinical drugs, drug-flavonoid interaction is becoming an increasingly important concern. This review article focused on the disposition of flavonoids and effects of flavonoids on relevant enzymes (e.g. UGTs and SULTs) and transporters (e.g. MRP2 and BCRP) involved in the interplay between phase II enzymes and efflux transporters. The effects of flavonoids on other metabolic enzymes (e.g. GSTs) or transporters (e.g. P-gp, OATP and OAT) are also addressed but that is not the emphasis of this review.

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Abstract: Dietary flavonoid-mediated induction of intestinal UGT1A1 may be important for the glucuronidation and detoxification of colon and other carcinogens as well as for the presystemic metabolism of therapeutic drugs.

Cited by 101 publications

References 20 publications

The Potential of Flavonoids to Influence Drug Metabolism and Pharmacokinetics by Local Gastrointestinal Mechanisms

The Potential of Flavonoids to Influence Drug Metabolism and Pharmacokinetics by Local Gastrointestinal Mechanisms

PhIP metabolites in human urine after consumption of well-cooked chicken

Mutual interactions between flavonoids and enzymatic and transporter elements responsible for flavonoid disposition via phase II metabolic pathways

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